Role of circadian rhythms in the susceptibility to Clostridium difficile infection

昼夜节律在艰难梭菌感染易感性中的作用

基本信息

批准号：
9895923
负责人：
Jerome Menet
金额：
$ 21.59万
依托单位：
TEXAS A&M UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-31 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9895923
关键词：
Accounting Adaptor Signaling Protein Address Affect Anaerobic Bacteria Animal Model Antibiotics Appearance Bile Acid Biosynthesis Pathway Bile Acids Biological Process Biology Cells Circadian Rhythms Clinical Clostridium difficile Community-Acquired Infections Cytoplasm Data Development Digestion Disease Environment Epidemic Epithelial Cells Exhibits Exposure to FZD1 gene Family Feedback Flow Cytometry Gene Expression Genes Genetic Transcription Genome Germination Goals Guanosine Triphosphate Phosphohydrolases Hospitals Impairment Infection Inflammation Inflammatory Response Leukocytes Light Mammalian Cell Mammals Mediating Metabolic Molecular Monitor Morbidity - disease rate Mus Nature Nosocomial Infections Organism Pathogenicity Pathologic Patients Periodicity Phase Physiology Predisposition Process Proteins Radiation Recovery Regulation Reproduction spores Resting Phase Role Severities Site Structure Symptoms Testing Time Toll-like receptors Toxic effect Toxin United States Virulence Wild Type Mouse bacterial resistance base circadian circadian pacemaker circadian regulation design differential expression experimental study feeding host colonization insight intestinal epithelium monocyte mortality mouse model poliovirus receptor receptor receptor expression recruit response rho rho GTP-Binding Proteins transcriptome sequencing virtual

项目摘要

Project Summary Clostridium difficile is now the most common cause of hospital-acquired infections in the United States. This Gram-positive, spore-forming, strict anaerobe most commonly infects antibiotic- treated hosts, though community-acquired infections are on the rise for unknown reasons. To survive outside a host, C. difficile produces dormant spores. Spores are metabolically dormant forms of bacteria that are resistant to many harsh conditions (e.g., many cleaning agents, heat, radiation and antibiotics). In a host, C. difficile spores germinate in response to bile acids. Following C. difficile spore germination, the vegetative cells produce the toxins that trigger the host’s inflammatory response and that cause the primary symptoms of disease. Remarkably, the effectors of C. difficile infection (e.g., toxin receptor abundance and inflammation) exhibit strong circadian rhythms. These rhythms are generated by molecular circadian clocks found in virtually every mammalian cell, and which rely on transcriptional feedback loops to coordinate the rhythmic expression of about 10-15% of the genome. The circadian nature of the host physiology suggests that the normal host circadian rhythms may impact the efficiency with which C. difficile infects, colonizes and causes disease. In this exploratory application, the effects of host circadian biology on the ability of C. difficile to colonize and on the host’s inflammatory response to C. difficile infection will be explored.

项目概要艰难梭菌现在是美国医院获得性感染的最常见原因这种革兰氏阳性、产芽孢、严格厌氧菌最常感染抗生素。尽管由于未知原因，社区获得性感染的治疗数量呈上升趋势。艰难梭菌在宿主体外生存，产生休眠孢子。孢子处于代谢休眠状态。对许多恶劣条件（例如许多清洁剂、热、在宿主中，艰难梭菌孢子响应胆汁酸而萌发。艰难梭菌孢子萌发后，植物细胞产生毒素，触发艰难梭菌孢子萌发。宿主的炎症反应并导致疾病的主要症状。艰难梭菌感染的效应物（例如毒素受体丰度和炎症）表现出强烈的昼夜节律是由分子生物钟产生的。几乎每个哺乳动物细胞都依赖转录反馈环来协调约 10-15% 基因组的节律表达宿主的昼夜节律性质。生理学表明，正常的宿主昼夜节律可能会影响效率艰难梭菌感染、定植并引起疾病。宿主昼夜节律生物学对艰难梭菌定殖能力和宿主的影响将探讨对艰难梭菌感染的炎症反应。